Preexistence and Clonal Selection of MET Amplification in EGFR Mutant NSCLC
Publication in refereed journal

香港中文大學研究人員

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其它資訊
摘要MET amplification activates ERBB3/PI3K/AKT signaling in EGFR mutant lung cancers and causes resistance to EGFR kinase inhibitors. We demonstrate that MET activation by its ligand, HGF, also induces drug resistance, but through GAB1 signaling. Using high-throughput FISH analyses in both cell lines and in patients with lung cancer, we identify subpopulations; of cells with MET amplification prior to drug exposure. Surprisingly, HGF accelerates the development of MET amplification both in vitro and in vivo. EGFR kinase inhibitor resistance, due to either MET amplification or autocrine HGF production, was cured in vivo by combined EGFR and MET inhibition. These findings highlight the potential to prospectively identify treatment naive, patients with EGFR-mutant lung cancer who will benefit from initial combination therapy.
著者Turke AB, Zejnullahu K, Wu YL, Song Y, Dias-Santagata D, Lifshits E, Toschi L, Rogers A, Mok T, Sequist L, Lindeman NI, Murphy C, Akhavanfard S, Yeap BY, Xiao Y, Capelletti M, Iafrate AJ, Lee C, Christensen JG, Engelman JA, Janne PA
期刊名稱Cancer Cell
出版年份2010
月份1
日期19
卷號17
期次1
出版社Elsevier (Cell Press)
頁次77 - 88
國際標準期刊號1535-6108
電子國際標準期刊號1878-3686
語言英式英語
Web of Science 學科類別Cell Biology; CELL BIOLOGY; Oncology; ONCOLOGY

上次更新時間 2020-20-11 於 00:04